interleukin-8 and Pleural-Effusion

This study was designed to test the hypothesis that measurement of IL-8 and CRP in pleural fluid could improve the identification of patients with non-purulent parapneumonic effusions that ultimately require chest tube drainage.. We assessed IL-8, CRP and three classical parameters (pH, glucose and LDH) in the pleural fluid of 100 patients with parapneumonic effusions. Forty-nine of these patients had non-purulent complicated effusions (complicated parapneumonic pleural effusion, CPPE), and 51 had uncomplicated parapneumonic pleural effusions (UPPE). Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid biochemical parameters for differentiating among the two patient groups. IL-8 production was determined using a commercially available ELISA kit, and CRP was measured by immunoassay.. At a cutoff value of 1000 pg/mL, IL-8 differentiated CPPE from UPPE with a sensitivity of 84% and a specificity of 82%. Likewise, CRP levels were higher in CPPE than in UPPE, and showed 72% sensitivity and 71% specificity at a cutoff value of 80 mg/L. We found that all five pleural fluid tests showed similar diagnostic accuracies when evaluated by receiver-operating characteristic analysis. However, multivariate analysis indicated that the size of the effusion, as well as pleural fluid pH and IL-8 concentration, were the best discriminatory parameters, with likelihood ratios of 6.4, 4.4 and 3.9, respectively.. Pleural fluid IL-8 is an accurate marker for the identification of non-purulent CPPE.

Topics: Adult; Aged; C-Reactive Protein; Community-Acquired Infections; Diagnosis, Differential; Female; Humans; Interleukin-8; Male; Middle Aged; Pleural Effusion; Pneumonia, Bacterial; Predictive Value of Tests; ROC Curve; Suppuration

We studied cytokine changes after video-assisted thoracoscopic lobectomy and conventional lobectomy in patients with stage IA lung cancer.. From June, 1997, 20 consecutive patients with stage IA non small-cell lung carcinoma underwent either conventional lobectomy via an open thoracotomy (n = 10) or video-assisted thoracoscopic lobectomy (n = 10). The cytokine concentration in serum and pleural fluid were measured for 6 days postoperatively.. Interleukin-6 and interleukin-8 leads peaked at 3 h or 1 day after surgery. Cytokine levels in pleural fluid were more than 100 times higher than corresponding systemic levels. The increase of interleukin-6 in pleural fluid 3 hours after surgery was significantly smaller in video-assisted thoracoscopic lobectomy (3971 +/- 2793 pg/mL for video-assisted thoracoscopic lobectomy vs. 23274 +/- 8426 pg/mL for open lobectomy). There were no significant differences in the serum interleukin-6 and interleukin-8 concentrations between the 2 groups.. The thoracoscopic approach lessened the increase of cytokines in pleural fluid, but benefits of reduced cytokine production in video-assisted thoracoscopy remain to be clarified.

Topics: Carcinoma, Small Cell; Female; Humans; Interleukin-6; Interleukin-8; Lung Neoplasms; Male; Middle Aged; Pleural Effusion; Pneumonectomy; Thoracic Surgery, Video-Assisted

Halting ventilation during cardiopulmonary bypass (CPB) is implemented to operate in a less bleeding setting. It sustains a better visualization of the operation area and helps to perform the operation much more comfortably. On the other hand, it may lead to a series of postoperative lung complications such as atelectasis and pleural effusion. In this study, we investigated the effects of low tidal volume ventilation on inflammatory cytokines during CPB.. Twenty-eight patients undergoing cardiovascular surgery were included in the study. Operation standards and ventilation protocols were determined and patients were divided into two groups: patients ventilated with low tidal volume and non-ventilated patients. Plasma samples were taken from patients preoperatively, perioperatively from the coronary sinus and postoperatively after CPB. IL-6, IL-8, TNF-α and C5a levels in serum samples were studied with enzyme-linked immunosorbent assay (ELISA) kits.. C5a, IL-6, IL-8 and TNF-α levels were similar when compared to the low tidal in volume ventilated and non-ventilated groups (P>0.05). Comparing the groups by variables, IL-6 levels were increased during CPB in both groups (P=0.021 and P=0.001), and IL-8 levels decreased in the ventilation group during CPB (P=0.018).. Our findings suggest that low tidal volume ventilation may reduce the inflammatory response during CPB. Although the benefit of low tidal volume ventilation in CPB has been shown to decrease postoperative lung complications such as pleural effusion, atelectasis and pneumonia, we still lack more definitive and clear proofs of inflammatory cytokines encountered during CPB.

Topics: Cardiopulmonary Bypass; Coronary Artery Bypass; Cytokines; Humans; Interleukin-6; Interleukin-8; Lung; Pleural Effusion; Postoperative Complications; Pulmonary Atelectasis; Tidal Volume; Tumor Necrosis Factor-alpha

We studied the diagnostic value of cytokines, including vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine deaminase (ADA) in pleural fluid.. Prospective analysis of 44 inpatients or outpatients with pleural fluid, from December 2016 to March 2017 was conducted.. We enrolled patients with malignant pleural effusion (MPE, N = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were significantly higher in empyema patients than in CRF/CHF or PPE patients. In all patients, the pleural fluid VEGF and IL-8 values were significantly positively correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-β was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA ratio in patients with MPE or empyema/PPE was significantly higher than in patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p < 0.001).. VEGF and IL-8 production in the pleural cavity appear to accelerate the progression of PPE to empyema, by enhancing vascular permeability associated with inflammation. Sequential sampling would be needed to confirm this. The pleural LDH/ADA ratio may be a useful diagnostic tool for discriminating between various pleural effusion etiologies.

Topics: Adenosine Deaminase; Aged; Aged, 80 and over; Biomarkers; Diagnosis, Differential; Empyema, Pleural; Female; Heart Failure; Humans; Interleukin-8; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Male; Middle Aged; Pleural Effusion; Pleural Effusion, Malignant; Pneumonia; Predictive Value of Tests; Prospective Studies; Transforming Growth Factor beta; Tuberculosis; Vascular Endothelial Growth Factor A

Thirty percent of patients with pneumonia develop pleural effusion, and of these, 20% have complicated effusion (CPPE), which may require a chest tube or surgery for resolution. The objective of the study is to compare the diagnostic yield of determining interleukin-1β and interleukin-8 in pleural fluid (PF) (PFIL-1β and PFIL-8) with respect to classic criteria (pH <7.2, lactate dehydrogenase [LD] >1,000 IU/mL, and/or glucose <60 mg/dL) in the early diagnosis of CPPE.. Of the 559 patients studied, 40 had CPPE. All underwent PF analysis: pH, glucose (PFGLUC), LD (PFLD), PFIL-1β and PFIL-8, and PF/serum ratios (PF/SIL-1β and PF/SIL-8).. The diagnostic criterion that showed the best area under the curve was the combination of PF/SIL-8 and PFIL-1β (0.906), with a statistically significant difference (P < .05) compared with the classic criterion of pH and PFGLUC or PFLD (0.826). The combination of PF/SIL-8 and PFIL-1β (cutoffs >5.73 and >9.14 pg/mL, respectively) was significantly more sensitive (72.7%) and more specific (97.9%) (P < .05) than the rest of the parameters used.. Measurement of IL-1β and IL-8 in pleural fluid may be useful in the early diagnosis of CPPE, although individually, it may not improve the results obtained with the PFLD. Further studies are needed to more firmly establish what role these new parameters can play in the diagnosis of CPPE.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Early Diagnosis; Empyema, Pleural; Glucose; Humans; Hydrogen-Ion Concentration; Interleukin-1beta; Interleukin-8; L-Lactate Dehydrogenase; Middle Aged; Pleural Effusion; Pleurisy; Pneumonia; ROC Curve; Sensitivity and Specificity; Young Adult

The objective of this study was to investigate inflammatory markers of the postpericardiotomy syndrome (PPS) and to determine individuals prone to develop the PPS.. The study included 75 patients with a stable coronary disease that had underwent coronary artery bypass surgery. Serum samples were collected prior to the surgery and on the 5th day after the operation, to measure the concentration of IL-8, IL-6, IL-1β, IL-10, TNF, IL-12p70. All included patients were screened for the PPS before discharge from the hospital and 6 months after the surgery. The 49 patients developed the PPS (65.4%), among them 42 (56%) patients had pleural effusion, and 23 (31%) had pericardial effusion. The cytokine analysis has shown an inverse correlation between IL-8 concentration before the surgery, and the occurrence of the PPS (p = 0.026). There were also positive correlations between the magnitude of increase of IL-8 and IL-1β concentrations on the 5th day after the surgery and the occurrence of the PPS (p = 0.006 and p = 0.049 respectively). Multivariate analysis revealed IL-8 concentration before surgery as an independent risk factor of the PPS development (HR = 0.976; 95%CI: 0.956-0.996, p = 0.02). Cut-off point was established to assess the predictive value of IL-8 concentration (21.1 pg/ml). The test parameters were: sensitivity: 62.5%, specificity: 75%, positive predictive value: 83% and negative predictive value: 50%. Clinical evaluation showed the relationship between the hemoglobin concentration before the surgery and the PPS occurrence (p = 0.01).. The IL-8 and IL-1β may participate in the postpericardiotomy syndrome pathogenesis, and the IL-8 concentration measurement may select patients with the risk of the PPS development.

Topics: Aged; Area Under Curve; Coronary Artery Bypass; Coronary Disease; Cytokines; Female; Hemoglobins; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Multivariate Analysis; Pericardial Effusion; Pleural Effusion; Postoperative Period; Postpericardiotomy Syndrome; Risk Factors; ROC Curve

To investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE) and their clinical importance.. From January 2008 through December 2010, 26 uncomplicated (UPPE) and 38 complicated (CPPE) PPE were studied. Based on chest ultrasonography, there were non-loculated in 30, uni-loculated in 12, and multi-loculated effusions in 22 patients. The effusion size radiological scores, and effusion vascular endothelial growth factor (VEGF), interleukin (IL)-8, plasminogen activator inhibitor type-1 (PAI-1) and tissue type plasminogen activator (tPA) were measured on admission. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up.. The effusion size and effusion VEGF, IL-8 and PAI-1/tPA ratio were significantly higher in CPPE than in UPPE, and significantly higher in multi-loculated PPE than in non-locualted and uni-loculated PPE, respectively. VEGF (cutoff value 1975 pg/ml) and IL-8 (cutoff value 1937 pg/ml) seemed best to discriminate between UPPE and CPPE. VEGF, IL-8 and effusion size correlated positively with PAI-1/tPA ratio in both UPPE and CPPE. Moreover, the level of VEGF, but not IL-8, correlated positively with effusion size in all patients (r = 0.79, p<0.001) and in UPPE (r = 0.64, p<0.001) and CPPE (r = 0.71, p<0.001) groups. The patients with higher VEGF or greater effusion were prone to have medical treatment failure (n = 10; VEGF, odds ratio 1.01, p = 0.02; effusion size, odds ratio 1.26, p = 0.01). Additionally, ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without.. In PPE, VEGF and IL-8 levels are valuable to identify CPPE, and higher VEGF level or larger effusion is associated with decreased fibrinolytic activity, development of pleural loculation and fibrosis, and higher risk of medical treatment failure.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cytokines; Female; Fibrinolysis; Follow-Up Studies; Humans; Interleukin-8; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Pleura; Pleural Effusion; Pneumonia; Tissue Plasminogen Activator; Treatment Outcome; Vascular Endothelial Growth Factor A

Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV-1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)-6, IL-8, interferon (IFN)-γ and transforming growth factor (TGF)-β, and did not include other T helper type 1 (Th1) (IL-2, IL-15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL-6 and IL-8, less with TGF-β, and not with IFN-γ. Among CD4 T cells, FoxP3-reactive CD25(hi) were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3(+) CD25(hi) CD4 T cells were positive for IL-8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV-1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL-6, IL-8, IFN-γ and TGF-β and regulatory T cells (T(reg) ). A correlation in expansion of T(reg) with proinflammatory cytokines (IL-6 and IL-8) in pleural fluid was shown. T(reg) themselves may promote the inflammatory cytokine milieu through IL-8.

Topics: Adult; Cytokines; Female; Forkhead Transcription Factors; Fusion Proteins, gag-pol; Gene Expression; HIV Infections; HIV-1; Humans; Interferon-gamma; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Plasma; Pleural Cavity; Pleural Effusion; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tuberculosis, Pleural; Viral Load; Young Adult

The aim of this study was to investigate the value and significance of interleukin-8 in differentiation of uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE). Using an IMMULITE 1000 Analyzer, with chemiluminescent immunometric assay, levels of interleukin-8 (IL-8) were measured in the pleural fluid of patients with UCPPE (n=30), and CPPE (n=30), and three classical parameters (pH, glucose, and LDH) in these two groups. Receiver-operating curves were to assess the sensitivity and specifity of interleukin-8 for differentiating between the two patient groups. IL-8 levels were statistically higher in the CPPE group. A positive significant correlation, was found between levels of IL-8 and and lactate dehydrogenase (LDH) (r=0.68, p<0.05). There was also a positive significant correlation between IL-8 and protein level in pleural effusion (r=0.306, r<0.01). There was a significant negative correlation between levels of IL-8 and pH (r=-0.83, p<0.05), and of IL-8 and glucose in pleural fluid (r=-0.61, p<0.05). A cut-off value of 1805.81 pg/ml, differentiated CPPE from UPPE with a sensitivity of 100% and a specifity of 98%. IL-8 may be used as an alternative marker for the complication of parapneumonic effusion.

Topics: Adult; Aged; Biomarkers; Diagnosis, Differential; Female; Glucose; Humans; Hydrogen-Ion Concentration; Interleukin-8; L-Lactate Dehydrogenase; Male; Middle Aged; Pleural Effusion; Pneumonia; Prognosis; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic

Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently.. To evaluate the pleural inflammatory response after surgery.. Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test.. All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1beta, IL-6, and IL-8 were undetectable at all time points.. There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.

Topics: Adult; Cytokines; Exudates and Transudates; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Liver Diseases; Lung Transplantation; Male; Middle Aged; Pleural Effusion; Postoperative Complications; Retrospective Studies; Vascular Endothelial Growth Factor A; Young Adult

Pleural effusion appears in approximately 40% of patients with pneumonia. Given that microbiology results are often negative, its diagnosis is frequently based on clinical criteria. Our study consisted of 266 patients, divided into infectious (n = 34), tuberculous (n = 54), paraneoplastic (n = 63), miscellaneous exudates (n = 53), and transudates (n = 62). Interleukin (IL)-6, IL-8, and IL-1beta were measured in the pleural fluid and serum of all patients, as well as the different cell populations in the pleural fluid. Analysis of the receiver operating characteristic curves of the different ILs in pleural fluid for the diagnosis of parapneumonic/empyematous effusion showed IL-6 with a sensitivity of 38.2% and specificity of 97.4%, IL-8 with a sensitivity of 73.5% and specificity of 65.1%, IL-1beta with a sensitivity of 55.6% and specificity of 91.3%, and total neutrophil count in pleural fluid (PNEU) with a sensitivity of 62.9% and specificity of 91.1%. The combination of IL-1beta and PNEU improved the yield, with a sensitivity of 75.7% and a specificity of 83.1%.

Topics: Adult; Aged; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Leukocyte Count; Male; Middle Aged; Neutrophils; Pleural Effusion; Retrospective Studies; Sensitivity and Specificity

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles.

Topics: Acute-Phase Reaction; Animals; Biomarkers; Injections; Interleukin-8; Kidney; L-Lactate Dehydrogenase; Leukocyte Count; Leukocytes; Liver; Lung; Neutrophils; Particle Size; Pleural Effusion; Pleurisy; Pleurodesis; Rabbits; Spleen; Talc; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation.. One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans's blue dye. Pleural fluid volume and cytokines were quantified.. Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab.. This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.

Topics: Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Capillary Permeability; Contraindications; Disease Models, Animal; Interleukin-8; Pleural Effusion; Pleurodesis; Rabbits; Silver Nitrate; Talc; Vascular Endothelial Growth Factor A

The differential diagnosis of pleural effusion is a frequent clinical problem. The possible role of pleural fluid cytokines in discriminating transudates from exudates has not been studied adequately. The aim of this study was to evaluate serum and pleural fluid levels of interleukin-8 (IL-8) and compare it with common biochemical parameters such as total protein lactate dehydrogenase (LDH). Forty patients with pleural effusion were studied. IL-8 was measured simultaneously in serum and pleural fluid using a commercially available ELISA kit. Standard laboratory methods were employed for biochemical parameters. Serum IL-8 levels were higher in the exudative group (8.1 +/- 0.2), but without statistical difference, when compared with transudate patients (6.8 +/- 0.1) (p > 0.05). Pleural IL-8 levels were significantly increased in exudate effusion when compared with transudate (26.6 +/- 3.7, 7.1 +/- 0.04 respectively, p < 0.001). In addition, a significant difference was found between pleural IL-8 in the malignant group (28.2 +/- 4.4) in comparison with the tuberculous group (21.1 +/- 2.9) (p < 0.01). Using ROC analysis, a pleural IL-8 cut off level of 19.7 pg/ml was found the best discriminating ratio in distinguishing exudates from transudates, with sensitivity of 100%, low specificity (from 50 to 66.7%) and good PPV (from 94.4 to 94.7%). Regarding pleural protein, the best discriminating value was 3 g/dl, while that for LDH was 200 IU/L. It is concluded that IL-8 could be considered as a sensitive, but not specific marker in differentiating pleural effusion into exudate and transudate, specially when used together with other criteria such as protein and LDH levels.

Topics: Adult; Aged; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Exudates and Transudates; Female; Humans; Inflammation Mediators; Interleukin-8; L-Lactate Dehydrogenase; Male; Middle Aged; Pleural Effusion; ROC Curve

To study the role of selected cytokines and growth factors involved in the pathogenesis of fetal chylous pleural effusion.. Seventeen fetuses with prenatal chylothorax at gestational age (GA) 17-29 weeks were enrolled as the study group during the period 2003-2005. Their pleural effusion (n = 17) and amniotic fluid (n = 17) were drawn when disease set in. Eleven fetuses received cordocentesis because of suspected fetal anemia. Forty-one normal fetuses without adverse perinatal outcome at GA 17-29 weeks received amniocentesis and were enrolled in the reference group. Levels of hepatocyte growth factor (HGF), stromal-derived factor-1(SDF-1), vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), macrophage migratory inhibition factor (MIF), and interleukin-6 (IL-6) were determined in the samples from both groups (amniotic fluid, pleural fluid, and cord blood from the study group and amniotic fluid from the reference group) by enzyme-linked immunoassay (EIA).. No significant differences were observed in the amniotic fluids between the study group and the reference group regarding levels of IL-6, IL-8, MIF, SDF-1, HGF and VEGF. In the study group, levels of IL-8, VEGF and SDF-1 (all pro-angiogenic) showed no significant differences between the amniotic fluid, cord blood and pleural effusion. The level of HGF (proangiogenic) was significantly higher in the amniotic fluid than in the cord blood or the pleural effusion, but there were no significant differences between the levels in the pleural fluid and in the cord blood. Interestingly, the levels of MIF and IL-6 (both are proinflammatory) in the amniotic fluid and in the pleural effusion were much higher than the levels in the cord blood.. Our study demonstrated that the levels of pro-inflammatory proteins (MIF and IL-6) that we tested were higher in the fetal pleural effusion than in the fetal circulation, a phenomenon not observed in the levels of proangiogenic proteins (HGF, SDF-1, VEGF, IL-8). This result implies that inflammation-related proteins may be more relevant than the angiogenesis-related proteins in the local environment of accumulating pleural effusion, a prominent feature of prenatal chylothorax.

Topics: Amniotic Fluid; Case-Control Studies; Chemokine CXCL12; Chemokines, CXC; Chylothorax; Female; Fetal Blood; Hepatocyte Growth Factor; Humans; Interleukin-6; Interleukin-8; Macrophage Migration-Inhibitory Factors; Male; Pleural Effusion; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Vascular Endothelial Growth Factor A

Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg.kg(-1)) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-beta1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis.

Topics: Animals; Dose-Response Relationship, Drug; Epithelial Cells; Inflammation; Interleukin-8; Male; Models, Animal; Pleural Effusion; Pleurodesis; Rabbits; Talc; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Progelatinase B/proMMP-9 has recently been identified as an indicator of pleural inflammation, presumably originating from granulocytes. The aim of this study was to verify the origin of progelatinase B by simultaneous estimation of specific markers of neutrophil recruitment and activation in pleural effusions following induced pleurisy and pleural injury.. Sixty-three samples of pleural fluid from patients undergoing therapeutic talc pleurodesis (n = 8) and explorative thoracoscopy (n = 3) collected before and at different time intervals after the intervention were analyzed for progelatinase B and neutrophil gelatinase-associated lipocalin (NGAL)-gelatinase complex by substrate electrophoresis, for myeloperoxidase (MPO) and interleukin-8 (IL-8) by immunoadsorbent sandwich assay, as well as for leukocyte count, C-reactive protein (CRP) and total protein (TP).. A significant increase in free and NGAL-complexed progelatinase B, MPO and IL-8 was recorded within 48 h following treatment in all subjects. Progelatinase B was strongly correlated with NGAL-gelatinase complex (r = 0.88, p = 0.001), MPO (r = 0.81, p = 0.001), neutrophil count (r = 0.75, p = 0.01) and IL-8 (r = 0.71, p = 0.001), but not with CRP and TP.. The results support the neutrophil origin of the proenzyme, which confirms progelatinase B as an indicator of a local inflammatory reaction. Quantifying the inflammatory reaction may be helpful in the evaluation of both the technical variants of therapeutic pleurodesis and finer discrimination of paraneoplastic effusions.

Topics: Acute-Phase Proteins; Aged; Biomarkers; Cell Degranulation; Collagenases; Enzyme Precursors; Female; Gelatinases; Humans; Interleukin-8; Lipocalin-2; Lipocalins; Male; Matrix Metalloproteinase 9; Metalloendopeptidases; Middle Aged; Neutrophils; Peroxidase; Pleura; Pleural Effusion; Pleurisy; Proto-Oncogene Proteins

Biochemical and inflammatory markers in pleural inflammation were evaluated in pediatric cases of parapneumonic effusions, and interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha concentrations were tested for possible differentiation of the complicated nature of effusions.. Twenty-eight patients (12 female) who were admitted to Hacettepe University Childrens' Hospital over a 2-year period were included in the study.. Patients were grouped according to the stage of effusion. Pleural fluid leukocyte count, neutrophil ratio, pH, protein, glucose levels, lactate dehydrogenase (LDH) levels, TNF-alpha levels, IL-8 levels, and nitrite levels were obtained.. Of these patients, 13 had empyema, 10 had complicated parapneumonic effusions (CPEs), and 5 had uncomplicated parapneumonic effusions (UPEs). Protein and glucose levels decreased, leukocyte count, neutrophil ratio, TNF-alpha levels, nitrite levels, and IL-8 levels increased progressively as the stage of the disease progressed. IL-8 levels, but not TNF-alpha and nitrite levels, were statistically different among the groups. IL-8, TNF-alpha, and nitrite levels all correlated positively with each other (all p < or = 0.001), and pH correlated negatively with these markers (all p < or = 0.001). At a cutoff value of 76.6 pg/mL, TNF-alpha discriminated between CPEs and UPEs with a sensitivity of 50%, a specificity of 100%, and an accuracy of 78%. At a cutoff value of 701.6 pg/mL, IL-8 differentiated CPE and UPE with a sensitivity of 80%, a specificity of 80%, and an accuracy of 86%.. Progressive changes in common biochemical markers (ie, pH, and protein, glucose, and LDH levels) are interrelated during stages of pleural inflammation. IL-8 may be used as an alternative marker for discriminating between CPEs and UPEs in pediatric parapneumonic effusions.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Interleukin-8; L-Lactate Dehydrogenase; Male; Nitric Oxide; Pleural Effusion; Pneumonia; Proteins; Tumor Necrosis Factor-alpha

To study the anti-inflammation effect of volatile oil of Centipeda minima and the mechanism of action.. The animal model was induced by the Car injection into intrapleural of rats, to observe the effect of VOCM on acute inflammation.. VOCM was able to inhibit the increase of NO, CRP and proinflammatory cytokines such as TNFalpha in the acute inflammation of the rat body.. VOCM has a protective effect on acute pleural effusion in rats induced by an intrapleural injection of Car.

Topics: Animals; Asteraceae; C-Reactive Protein; Carrageenan; Dinoprostone; Interleukin-8; Leukocyte Count; Male; Nitric Oxide; Oils, Volatile; Plants, Medicinal; Pleural Effusion; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

s: To determine whether talc (TL) and silver nitrate (SN), two effective pleurodesis agents, induce a systemic inflammatory response in the acute phase of experimental pleurodesis in rabbits.. Samples of blood and pleural fluid were collected after 6, 24, and 48 h from rabbits injected intrapleurally with 3 mL saline solution, TL (400 mg/kg), or 0.5% SN, and were assayed for WBC count, percentage of neutrophils, and levels of lactate dehydrogenase (LDH), interleukin (IL)-8, and vascular endothelial growth factor (VEGF). The pleural liquid production was compared in the three different groups. A sample of blood collected from animals preinjection was used as the control.. At 6 h after pleural injection, the mean blood WBC count and percentage of neutrophils were significantly elevated in the TL group, whereas the mean LDH and IL-8 levels were significantly increased in the SN group. VEGF was undetectable in the preinjection serum and saline solution-injected animals, but was increased in the serum after the pleural injection of both TL and SN to a comparable degree. SN elicited a more intense acute pleural inflammation reaction than did TL, with higher WBC count and IL-8 levels found in the pleural fluid, mainly within the first 6 h. LDH and VEGF levels, and pleural liquid production were also higher for SN, and they increased with time.. In the acute phase of pleural injection, TL induced a transient increase in blood WBC count and percentage of neutrophils, while SN induced increases in blood LDH and IL-8 levels. Both TL and SN induced significant increases in blood VEGF levels. SN induced an earlier and more intense acute pleural inflammation than TL. Pleural liquid VEGF levels were higher after SN injection and increased, as did pleural liquid production. These findings suggest that the intrapleural injection of TL and SN produce a systemic inflammatory response that may have a role in the pathogenesis of fever and ARDS, which occur with pleurodesis.

Topics: Acute Disease; Animals; Disease Models, Animal; Inflammation; Inflammation Mediators; Injections, Intralesional; Interleukin-8; Leukocyte Count; Male; Pleural Effusion; Pleurodesis; Rabbits; Random Allocation; Reference Values; Sensitivity and Specificity; Silver Nitrate; Talc; Vascular Endothelial Growth Factor A

Interleukin-8 (IL-8) plays an important role in the host immune response to Mycobacterium tuberculosis by recruiting inflammatory cells to the site of infection. Here, we investigated the role of pleural macrophages and mesothelial cells in the production of IL-8 in tuberculous pleurisy. Large concentrations of IL-8 were detected in tuberculous pleural effusions, but not in pleural effusions associated with congestive heart failure (CHF). Tuberculous pleural macrophages and M. tuberculosis-infected CHF pleural macrophages produced large concentrations of IL-8. When immunohistochemistry was performed on pleural tissues, antigenic IL-8 was detected in the mesothelial cells lining the tuberculous pleura. Direct stimulation of cultured CHF pleural mesothelial cells with M. tuberculosis induced IL-8 secretion. However, conditioned media from M. tuberculosis-infected pleural macrophages (CoMTB) induced greater mesothelial cell IL-8 secretion. Tumour necrosis factor-alpha (TNF-alpha) and IL-1beta induced mesothelial cell IL-8 mRNA expression, and neutralizing anti-TNF-alpha antibody and IL-1 receptor antagonist nearly completely obliterated CoMTB-induced mesothelial cell IL-8 mRNA expression and protein secretion. These findings demonstrate that both pleural macrophages and mesothelial cells produce IL-8 in tuberculous pleurisy, and cytokines produced by M. tuberculosis-infected macrophages mediate mesothelial cell IL-8 production.

Topics: Adult; Aged; Antibodies, Monoclonal; Cells, Cultured; Chemotaxis, Leukocyte; Epithelial Cells; Female; Heart Failure; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-8; Macrophages; Male; Middle Aged; Pleura; Pleural Effusion; RNA, Messenger; Sialoglycoproteins; Tuberculosis, Pleural; Tumor Necrosis Factor-alpha

The response of the fibrinolytic system to inflammatory mediators in empyema and complicated parapneumonic pleural effusions is still uncertain. We prospectively analysed 100 patients with pleural effusion: 25 with empyema or complicated parapneumonic effusion, 22 with tuberculous effusion, 28 with malignant effusion and 25 with transudate effusion. Inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and polymorphonuclear elastase, were measured in serum and pleural fluid. Fibrinolytic system parameters, plasminogen, tissue-type plasminogen activator (t-PA) and urokinase PA, PA inhibitor type 1 (PAI 1) and PAI type 2 concentrations and PAI 1 activity, were quantified in plasma and pleural fluid. The Wilcoxon signed-rank test was used to compare plasma and pleural values and to compare pleural values according to the aetiology of the effusion. The Pearson correlation coefficient was used to assess the relationship between fibrinolytic and inflammatory markers in pleural fluid. Significant differences were found between pleural and plasma fibrinolytic system levels. Pleural fluid exudates had higher fibrinolytic levels than transudates. Among exudates, tuberculous, empyema and complicated parapneumonic effusions demonstrated higher pleural PAI levels than malignant effusions, whereas t-PA was lowest in empyema and complicated parapneumonic pleural effusions. PAI concentrations correlated with TNF-alpha, IL-8 and polymorphonuclear elastase when all exudative effusions were analysed, but the association was not maintained in empyema and complicated parapneumonic effusions. A negative association found between t-PA and both IL-8 and polymorphonuclear elastase in exudative effusions was strongest in empyema and complicated parapneumonic effusions. Blockage of fibrin clearance in empyema and complicated parapneumonic effusions was associated with both enhanced levels of PAIs and decreased levels of t-PA.

Topics: Empyema, Pleural; Exudates and Transudates; Fibrinolysis; Humans; Inflammation Mediators; Interleukin-8; Leukocyte Elastase; Plasminogen; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Pleural Effusion; Pleural Effusion, Malignant; Prospective Studies; Statistics, Nonparametric; Tissue Plasminogen Activator; Tuberculosis, Pleural; Tumor Necrosis Factor-alpha; Urokinase-Type Plasminogen Activator

An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNFalpha and IFNgamma levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0.770, 0.875, 0.892 and 0.987, respectively for IL-8, TNFalpha, ADA and IFNgamma. No false-positives were encountered with IFNgamma and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFNgamma is a very reliable marker of tuberculous pleurisy.

Topics: Adenosine Deaminase; Aged; Area Under Curve; Biomarkers; Female; Humans; Interferon-gamma; Interleukin-8; Male; Pleural Effusion; Pleural Effusion, Malignant; Pleurisy; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Statistics, Nonparametric; Tuberculosis, Pleural; Tumor Necrosis Factor-alpha

In order to investigate the role of eotaxin in pleural diseases, we measured eotaxin in pleural effusions and studied the relationship between eotaxin levels and recruitment of inflammatory cells, particularly eosinophils. Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) levels were also measured for comparison.. We evaluated 47 pleural effusion samples, 7 transudates and 40 exudates. The exudates consisted of 19 malignant, 11 tuberculous, and 5 parapneumonic effusions, and 5 effusions of other etiologies. Chemokine levels were measured by specific sandwich enzyme-linked immunosorbent assays.. Eotaxin was detected in all samples examined, but the levels did not differ significantly among the exudates. There was no significant correlation between the levels of eotaxin and MCP-1 or IL-8. The level of eotaxin but not the others was significantly higher in eosinophilic effusions (>10% eosinophils among white blood cells in the fluid) than in non-eosinophilic fluids. The number of eosinophils in pleural effusions was significantly correlated with the eotaxin levels, but not with the levels of other chemokines. The number of neutrophils was significantly correlated with IL-8 but not with the others.. Results suggest that eotaxin contributes to the migration of eosinophils in pleural inflammation. Taken together with the correlation between IL-8 and neutrophils, it appears that the predominant type of pleural inflammatory infiltrate is controlled, at least in part, by the subgroup of chemokines expressed in the pleural space.

Topics: Chemokine CCL11; Chemokine CCL2; Chemokines; Chemokines, CC; Chemotactic Factors, Eosinophil; Cytokines; Eosinophils; Humans; Interleukin-8; Monocytes; Pleural Diseases; Pleural Effusion

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.

Topics: Acute Disease; Adolescent; Adult; Bronchoalveolar Lavage Fluid; Case-Control Studies; Chest Pain; Child; Child, Preschool; Cytokines; Duffy Blood-Group System; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Male; Pleural Effusion; Polymerase Chain Reaction; RNA, Messenger; Sickle Cell Trait; Syndrome

The pleural space is a potential compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells in a number of respiratory diseases. In an attempt to understand one aspect of the inflammatory process in the pleural space, we compared the responses in three different diseases (congestive heart failure [CHF], tuberculosis [TB], and cancer). Large concentrations of interleukin-8 (IL-8) were detected in cancer and TB effusions, but not in CHF. Surprisingly, the concentration of IL-8 correlated best with lymphocyte recruitment and not with neutrophil recruitment. Pleural fluid from cancer and TB patients was chemotactic for lymphocytes, and this activity was partly blocked by an anti-IL-8 antibody in cancer and completely blocked in TB. To determine whether there was the potential for a chemotactic gradient into the pleural space, pleural effusion cells were analyzed for the expression of IL-8. Cells in the effusions of cancer patients expressed IL-8, whereas IL-8 could not be detected from the cells of TB and CHF effusions. To explore the possible role of pleural macrophages in the regulation of IL-8, pleural effusion cells were treated with culture supernatants from stimulated pleural macrophages. Stimulated pleural macrophages were able to induce expression of messenger RNA (mRNA) for IL-8 and IL-8 protein production, and this activity was abrogated by blocking tumor necrosis factor-alpha. These findings suggest that soluble IL-8 is an important factor for the recruitment of lymphocytes into the pleural space, and that this cytokine is produced by both pleural structural and cancer cells after their activation by macrophage-derived, cytokine-mediated signals.

Topics: Adult; Aged; Body Fluids; Chemotaxis, Leukocyte; Heart Failure; Humans; Interleukin-8; Lymphocytes; Macrophages; Middle Aged; Neoplasms; Osmolar Concentration; Pleura; Pleural Effusion; Tuberculosis

To determine the prognostic value of various cytokine levels in ascites and pleural effusion during the evolution of severe ovarian hyperstimulation syndrome (OHSS).. A longitudinal study.. University teaching hospital.. Twenty patients with severe OHSS who required either paracentesis or thoracentesis or both from whom ascites (n = 56) or pleural effusion (n = 12) samples were obtained. Control peritoneal fluid was obtained from 20 patients undergoing ovarian stimulation for IVF.. Abdominal paracentesis for tense ascites and thoracentesis for massive pleural effusion. Control peritoneal fluid was obtained before oocyte retrieval.. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), E2, and progesterone concentrations in ascites and pleural effusion.. Levels of VEGF and IL-6 in ascites dropped significantly during the course of OHSS and were not correlated with E2 concentrations. Levels of VEGF were significantly correlated with levels of IL-1 beta, IL-8, and TNF-alpha, as well as progesterone concentrations, hematocrit, and white blood cell counts. None of the cytokine levels measured in pleural effusion were correlated with the course of OHSS.. These results suggest that local cytokines might be involved in the evolution of severe OHSS and possibly serve as prognostic markers for this syndrome.

Topics: Adult; Ascites; Cytokines; Drainage; Endothelial Growth Factors; Female; Fertilization in Vitro; Humans; Insemination, Artificial; Interleukin-1; Interleukin-6; Interleukin-8; Lymphokines; Ovarian Hyperstimulation Syndrome; Paracentesis; Pleural Effusion; Prognosis; Punctures; Time Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Malignant pleural mesothelioma (MPM), despite current therapeutic strategies, is still an aggressive tumor with a very poor prognosis. Interleukin-8 (IL-8), a proinflammatory and angiogenic cytokine, has an important role in tumor-related neovascularization. IL-8 has also been described to function as an autocrine growth factor. The purpose of this study was to evaluate the effect of IL-8 antibody (IL-8 Ab) on progression of MPM in vivo. Athymic nude mice (n = 65) were injected intrapleurally with human MPM cells (CRL-2081), equally divided into three groups (IL-8 Ab, control Ab, untreated), and received IP injection of IL-8 Ab, control Ab, or no treatment, respectively, every 48 h up to 15 days. Pleural fluid and serum IL-8 levels, and tumor and body weight of mice were measured following 5, 10, and 15 days of tumor injection. We found that both pleural fluid and serum IL-8 levels were significantly (P < 0.0001) lower in mice that received IL-8 Ab when compared to the other groups. In this group, lower IL-8 levels were associated with a decreased rate of tumor growth. There was a significant and direct correlation between pleural fluid IL-8 levels and tumor weight of all animals enrolled in this study (P < 0.0001, r = 0.88). We demonstrate that antibody treatment against IL-8 decreased human MPM progression. Our results suggest that treatments targeting the decrease of MPM-associated IL-8 levels or the effects of this protein may inhibit mesothelioma growth.

Topics: Animals; Antibodies, Monoclonal; Body Weight; Humans; Immunohistochemistry; Interleukin-8; Leukocyte Count; Male; Mesothelioma; Mice; Mice, Nude; Pleural Effusion; Pleural Neoplasms

Sclerosants such as tetracycline (TCN) have often been used in the control of malignant pleural effusions. Although the resultant inflammatory response is probably important in the ensuing pleural fibrosis, the signals responsible for the cellular influx into the pleural space following TCN instillation are not well understood. This study, therefore, sought to determine whether the chemokines interleukin-8 (IL-8), growth-related protein (Gro), and monocyte chemotactic protein-1 (MCP-1) were locally elaborated within the first 72 h following intrapleural TCN administration. TCN induced an exudative effusion with high lactate dehydrogenase activity. Although there was no significant change in the pleural fluid total leukocyte content, the median polymorphonuclear neutrophil concentration decreased from 1.067x10(6) to 2.03x10(5) cells x mL(-1) between 24 and 72 h, whereas the median macrophage concentration increased from 1.44x10(5) to 5.98x10(5) cells x mL(-1) over the same period. Furthermore, IL-8, Gro and MCP-1 concentrations decreased between 24 and 72 h. Immunocytochemistry indicated expression of IL-8 by pleural mesothelial cells 24 h, but not 72 h, following TCN administration. The data suggest that local elaboration of interleukin-8 and growth-related protein, in part of mesothelial origin, may influence neutrophil recruitment in tetracycline-induced pleuritis.

Topics: Analysis of Variance; Animals; Chemokine CCL2; Chemokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Immunohistochemistry; Interleukin-8; Leukocyte Count; Neutrophils; Nuclear Proteins; Pleural Effusion; Pleurisy; Rabbits; Statistics, Nonparametric; Tetracycline

Defensins, also known as human neutrophil peptides, are antimicrobial peptides present in the azurophil granules of neutrophils. We measured their level in pleural effusion in various pulmonary diseases to investigate whether they could be used as a diagnostic marker in the differential diagnosis of specific pleural diseases.. We analyzed pleural effusion samples collected from 61 patients, including 50 exudates (11 with empyema, 3 parapneumonic, 15 tuberculous, 18 neoplastic, 3 miscellaneous) and 11 transudates as controls.. Defensins were measured by radioimmunoassay and also analyzed by reverse-phase high-performance liquid chromatography. The concentrations of interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) in pleural effusion fluid were measured by enzyme-linked immunosorbent assay to examine the correlation between these cytokines and defensins.. The concentration of defensins in all samples of empyema was >5,100 ng/mL and the mean concentration (13,265.8+/-1,895.2 ng/mL) in these samples was the highest among other groups. The concentration in the other 50 pleural effusion samples tested was <2,800 ng/mL. Defensins were mostly of the mature type in empyema. Pleural effusion levels of IL-8 and G-CSF in patients with empyema were also significantly higher than those in other samples. There was a significant correlation between defensins and IL-8 or G-CSF in pleural effusion fluid (r=0.762, and 0.827, respectively).. Our results suggest that the high effusion concentrations of defensins in pleural effusion may constitute an important component of the host defense system or may have a cytotoxic role in empyema. Our results also indicate that the high levels of IL-8 and G-CSF in empyema may indirectly explain the elevated levels of defensins by increasing the number of neutrophils in the pleural space.

Topics: Biomarkers; Blood Proteins; Chromatography, High Pressure Liquid; Defensins; Diagnosis, Differential; Empyema, Pleural; Empyema, Tuberculous; Enzyme-Linked Immunosorbent Assay; Female; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Pleural Effusion; Pleural Effusion, Malignant; Pneumonia; Radioimmunoassay

Increased levels of interleukin-6 (IL-6) and IL-8 are found in various immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3 +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml-1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8: 450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/- 1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of active disease. The low levels of sIL-6R in the presence of high levels of IL-6 in pleural effusions, and the high levels of sIL-6R in the presence of low levels of IL-6 in serum suggest that the expression or shedding of sIL-6R may be downregulated in the presence of excessive amounts of IL-6.

Topics: Adult; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Male; Pleural Effusion; Receptors, Interleukin-6; Statistics, Nonparametric; Tuberculosis, Pleural

In order to know the degree of interleukin-8 (IL-8) production in the pleural space and its relationship to neutrophil activation, IL-8, neutrophil elastase (NE), and myeloperoxidase (MPO) were assessed in blood and pleural fluid (PF) of 219 patients with pleural effusions. Correlations between blood and PF IL-8, NE, and MPO were either absent or weak, except for IL-8 in transudates (r = 0.6745, p < 0.001). PF IL-8, NE, and MPO concentrations in cases of empyema were higher than in cases of effusion of other causes (p < 0.001). No significant differences in inflammatory markers were observed between parapneumonic and tuberculous fluids. IL-8, NE, and MPO levels in malignant, nonspecific, and transudative effusions were lower than in those due to infection, the lowest levels corresponding to transudates. No significant correlation was observed between PF IL-8 and neutrophil count in any group; in contrast, IL-8 was associated with NE and MPO in empyema (r = 0.7545, and r = 0.7283; p < 0.001), tuberculosis (r = 0.4016, p = 0.008 and r = 0.6545, p < 0.001), and nonspecific effusions (r = 0.3748, p = 0.007 and r = 0.3085, p = 0.028). Our results indicate that local production of markers of the nonspecific inflammatory response is high in both chronic and acute pleural infection, and suggest a role for IL-8 in the release of NE and MPO.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Inflammation Mediators; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Male; Middle Aged; Neutrophils; Peroxidase; Pleural Effusion

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 +/- 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 +/- 1,993 vs. 9,438 +/- 1,407 pg/ml: p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 +/- 176 vs. 10.2 +/- 1.3 pg/ml, p < 0.0001; IL-8: 319 +/- 85 vs. 9.6 +/- 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 +/- 1.3 pg/ml) in comparison to controls (7.3 +/- 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 +/- 1.5 pg/ml; all values are mean +/- SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression of sIL-6R shedding in the presence of excessive amounts of IL-6.

Topics: Aged; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Lung Neoplasms; Male; Middle Aged; Pleural Effusion; Pleurisy; Receptors, Interleukin-6

Treatment of symptomatic carcinomatous pleural effusions is primarily directed at local palliation with a wide variety of sclerosing agents, of which talc is considered to be the most successful. The mechanism whereby talc achieves this effect is unknown. The objective of this study was to investigate whether talc stimulates pleural mesothelial cells (PMC) to release C-X-C and/or C-C chemokines and express adhesion molecules that initiate and amplify the inflammatory process in the pleural space. When PMC were challenged with talc in vitro, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) levels were increased (p < 0.001) both at the protein and the mRNA level as compared with unstimulated cultures. Talc-stimulated PMC culture supernatant showed chemotactic activity for neutrophils and monocytes. The chemotactic activity of PMC culture supernatant was blocked by 44.2% with IL-8-specific antibody and by 55.7% with MCP-1-specific antibody, demonstrating that PMC-derived chemokines are bioactive. Talc also enhanced intercellular adhesion molecule-1 (ICAM-1) expression in PMC. The data demonstrate that talc stimulates PMC to release chemokines and express adhesion molecules that may play a critical role in pleurodesis.

Topics: Analysis of Variance; Antibodies; Cells, Cultured; Chemokine CCL2; Chemokines, CC; Chemokines, CXC; Chemotaxis, Leukocyte; Epithelial Cells; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Monocytes; Neutrophils; Pleura; Pleural Effusion; Pleurodesis; RNA, Messenger; Sclerosing Solutions; Talc

Talc administration into the pleural cavity induces pleurodesis. To obtain further insight into the inflammatory process that causes pleurodesis, the cellular kinetics in the pleural space after the administration of talc was studied, along with its relation to chemokine concentrations in the pleural fluid. Thirteen consecutive patients with idiopathic spontaneous pneumothorax and eight patients with malignant pleural effusions received talc pleurodesis. The first group was treated with talc poudrage, whereas the second group was treated with talc slurry. Pleural fluids were isolated before talc administration as well as 3, 6, 24, 48 and 72 h afterwards. The talc induced a rapid polymorphonuclear neutrophil (PMN) influx followed by an accumulation of macrophages. In addition, increased production of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 was observed. The talc-induced PMN influx reached its maximum after 3-24 h, and was related to the IL-8 concentration. In contrast, the MCP-1 was not related to the macrophage accumulation. Talc-induced inflammation in patients with idiopathic spontaneous pneumothorax and malignant pleural effusion is characterized by an influx of polymorphonuclear neutrophils related to interleukin-8, followed by an accumulation of monocytes.

Topics: Adult; Chemokine CCL2; Female; Humans; Inflammation; Interleukin-8; Leukocyte Count; Macrophages; Male; Neutrophils; Pleura; Pleural Effusion; Pleural Effusion, Malignant; Pleurodesis; Pneumothorax; Talc

Our study investigated the presence of IL-8 in pleural exudates from tuberculosis patients (TBP) (n = 13), and evaluated whether it was related with the profile of major immunocompetent cells present in their pleural and peripheral compartments. To allow comparisons, an additional group of patients with parapneumonic pleural effusions (PNE) (n = 7) was included. Blood peripheral immunophenotypic studies were also carried out in 12 age-matched healthy controls (Co), and 39 tuberculosis patients classified, according to the extent of pulmonary involvement, into mild (n = 9), and advanced (n = 30) cases. Patients were recruited before starting therapy, had HIV negative serology, and showed no age differences among groups (mean +/- SD., 40.7 +/- 14.7 years). IL-8 concentrations were measured by an ELISA method while immunophenotypic analysis was performed by using FITC-conjugated monoclonal antibodies reacting against the following cell surface molecules: CD3, CD4, CD8, CD25 (IL-2R+ cells), CD19, and CD68. IL-8 was detected in all pleural exudates though levels in the TB patients, 384 +/- 110 pg/ml, appeared significantly higher than the PNE group, 185 +/- 110 pg/mg, (P < 0.015, mean +/- S.D.). In turn, the former group presented values of pleural CD3+, CD4+, and CD25, which were found increased in comparison with PNE patients (P < 0.01). Unlike the pleural compartment, patients with TBP showed a marked and significant decrease in their circulating levels of cells bearing the CD3, CD4, CD19, CD25, and CD68 phenotypes not only when comparing with Co but also with PNE and mild patients. Differences between the levels of pleural and peripheral T-cells from TBP patients may be the reflection of an important influx of T-lymphocytes from the circulatory system to the pleural cavity, probably linked to the presence of chemotactic factors within the pleural fluid like IL-8.

Topics: Adolescent; Adult; Aged; Chemotaxis, Leukocyte; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunocompetence; Immunophenotyping; Interleukin-8; Lymphocyte Count; Lymphocyte Subsets; Male; Middle Aged; Pleural Effusion; Pneumonia; Tuberculosis, Pleural; Tuberculosis, Pulmonary

The balance between proinflammatory cytokines and their inhibitors has rarely been investigated in pleural effusions of nonmalignant or noninfectious origin. To evaluate the impact of a lung and/or intrathoracic infection in such a circumstance, we compared the levels of proinflammatory cytokines (interleukin-8 [IL-8]); tumor necrosis factor-alpha (TNF-alpha); the cytokine antagonists and inhibitors (IL-1 receptor antagonist [IL-1ra]) and soluble TNF receptors Types I and II (sTNFRI, sTNFRII); and antiinflammatory cytokines (transforming growth factor-beta [TGF-beta]) in pleural effusion and plasma from septic (n = 15) and nonseptic (n = 9) patients. In addition, we analyzed the levels of IL-6 and its soluble receptor (sIL-6R). Bronchoalveolar lavage fluids (BALFs) were also studied in a few septic patients. High and nonsignificantly different levels of cytokines and inhibitors were detected in both groups of patients. The levels of IL-6 and sTNFRI and sTNFRII in pleural effusion were higher than in plasma, whereas the levels of IL-1ra and sIL-6R were higher in plasma. The levels of sIL-6R influenced the bioactivity of IL-6. There was no correlation between the levels of cytokines in plasma and in pleural effusion. In contrast, a significant correlation was observed for the soluble receptors sIL-6R (r = 0.67, p < 0.001), sTNFRI (r = 0.76, p < 0.001) and sTNFRII (r = 0.66, p = 0.001). Furthermore, a high correlation was found between the levels of both forms of sTNFRs in plasma (r = 0.95, p < 0.001) and in pleural effusion (r = 0.79, p < 0.001). In addition, a correlation was observed between the levels of TGF-beta in pleural effusion and in BALF. The highest levels of some markers in plasma and of others in pleura argue in favor of both a systemic and a compartmentalized response, independently of the presence of infection. Because cytokines can be trapped by the surrounding cells in their environment, measurable levels of cytokines in biologic fluids represent the "tip of the iceberg," which is not the case for soluble receptors. The correlations of these latter markers between plasma and pleura strongly suggest that exchanges between both compartments can occur in both directions.

Topics: Adult; Aged; Aged, 80 and over; Biological Assay; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Pleural Effusion; Receptors, Cytokine; Receptors, Interleukin-1; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor; Sepsis; Solubility; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

The objective of this study was to follow the kinetics of four inflammatory cytokines in the plasma and ascitic fluid of seven patients who developed severe ovarian hyperstimulation syndrome (OHSS) after induction of ovulation for in-vitro fertilization. Blood samples were obtained from these patients at three different times: upon hospitalization; when significant clinical improvement was evident; and after complete resolution. Samples were analysed for interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-alpha). Ascitic fluid was obtained by therapeutic paracentesis from all study patients during the active phase and analysed for these cytokines. Two control groups were available: the first included 15 women undergoing controlled ovarian stimulation for in-vitro fertilization without developing OHSS, while the second consisted of 25 healthy women not undergoing ovulation induction or any other medical treatment. High concentrations of IL-1, IL-6 and TNF-alpha were detected in all individuals upon admission for severe OHSS. Concentrations dropped significantly along with clinical improvement, reaching normal values after complete resolution. A statistically significant correlation was found between plasma cytokine concentrations and certain biological characteristics of the syndrome such as leukocytosis, increased haematocrit, and elevated plasma 17-beta-oestradiol concentrations. Ascitic fluid obtained from the study patients contained high IL-6 and IL-8 concentrations, while other cytokines were unaltered. These results suggest close association between inflammatory cytokines and the pathophysiology of the ovarian hyperstimulation syndrome.

Topics: Adult; Ascitic Fluid; Case-Control Studies; Cytokines; Female; Fertilization in Vitro; Humans; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Kinetics; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pleural Effusion; Tumor Necrosis Factor-alpha

Leukaemia inhibitory factor (LIF), a pleiotropic cytokine detected in various inflammatory body fluids, plays a poorly defined role in the pathogenesis of human disease. This study was conducted to correlate the LIF concentrations in pleural effusions with the type of pathology and to compare its levels with those of IL-4, IL-8, IL-10 and M-CSF for a given pathology. Pleural fluids from 97 patients were assayed for cytokines by specific ELISAs. The concentrations of all cytokines tested were higher in infectious pleural effusions than in other pathologies (malignant or transudative). The lowest levels were observed for transudates. Significant differences were noted between pathology groups for each cytokine. A good correlation was observed between LIF and IL-8 for malignant effusions [regression correlation coefficient (RC) = 0.480, P < 0.01], between LIF and IL-4 for infectious disorders (RC = 0.543, P < 0.05) between LIF and IL-10 for transudates (RC = 0.798, P < 0.001) and between M-CSF and IL-8 in all pathologies tested except for primitive neoplasia (P < 0.05). The LIF concentration in pleural space seems to be strongly associated with the intensity of inflammatory reaction. The LIF production appears to have different regulatory patterns between aetiologic groups.

Topics: Aged; Enzyme-Linked Immunosorbent Assay; Female; Growth Inhibitors; Humans; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Leukemia Inhibitory Factor; Lymphokines; Macrophage Colony-Stimulating Factor; Male; Middle Aged; Pleural Effusion

Interleukin-8 (IL-8) is a recently described potent chemotactic factor that may be involved in the pathogenesis of pleural effusions. To understand the actual mechanisms mediating the inflammatory response, changes in cellular components and IL-8 level in pleural fluid of different aetiologies were evaluated. Thirty-four patients (19 male, 15 female) with a mean age of 46 +/- 22 years (range 16-92) were included in the study. Of these, 13 had tuberculous pleural effusion, seven had empyema/parapneumonic pleural effusion, and 14 had malignant pleural effusion (seven adenocarcinoma, three ovarian carcinoma, two lymphoma, one chronic myeloid leukaemia, and one small cell carcinoma) with positive cytology. Differential cell counts in the pleural fluid were obtained using cytocentrifuge preparations. The concentrations of IL-8 in pleural fluid were measured by the ELISA method. Interleukin-8 was detected in all 34 pleural fluid samples. The serum IL-8 level was analysed only in the empyema/parapneumonic pleural effusion group. The mean IL-8 levels of tuberculous, empyema/parapneumonic, and malignant pleural effusions were 1420 +/- 1049 pg ml-1, 4737 +/- 2297 pg ml-1, and 1574 +/- 1079 pg ml-1, respectively. The IL-8 levels in the empyema/parapneumonic group were significantly raised over malignant and tuberculous groups (P < 0.02). The mean pleural fluid neutrophil counts in tuberculous, empyema/parapneumonic and malignant pleural effusions were 315 +/- 575 cells mm-3, 11,136 +/- 12,452 cells mm-3, and 635 +/- 847 cells mm-3, respectively (P < 0.003). There was a significant positive correlation between pleural IL-8 levels and neutrophil counts (r = 0.46, P < 0.006). The levels of IL-8 in paired samples of serum and pleural fluid in the empyema/parapneumonic effusion group were compared, and the concentration of IL-8 was higher in the pleural effusion than serum (means, 4737 +/- 2297 pg ml-1 and 130.0 +/- 62.5 pg ml-1, respectively, P < 0.03). There was a significant negative correlation between IL-8 concentrations in serum and pleural fluid (r = -0.80, P < 0.03). This data suggests that production of IL-8 in pleural effusion may play a key role in initiation and maintenance of inflammatory reactions, especially in empyema/parapneumonic pleural effusions. It may offer the basis for introduction of novel anti-inflammatory agents in treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Empyema, Pleural; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Leukocyte Count; Male; Middle Aged; Neutrophils; Pleural Effusion; Pleural Effusion, Malignant; Tuberculosis, Pleural

Pleural effusions secondary to various diseases are associated with the presence of different inflammatory cells. The role of selective chemotactic cytokines in the recruitment of phagocytes to the pleural space is unclear. IL-8 and monocyte chemotactic peptide-1 (MCP-1) are recently described cytokines that are chemotactic for neutrophils and monocytes, respectively. We prospectively studied 63 patients, using strictly defined criteria for their selection. IL-8 concentrations were elevated in both empyema fluid (9.15 +/- 0.89 ng/ml) and parapneumonic effusions (4.7 +/- 0.697 ng/ml) when compared with pleural effusions secondary to other diseases. IL-8 levels were higher in empyema fluid than in parapneumonic effusions (p = 0.01). There was a significant correlation between IL-8 levels and the total numbers of neutrophils in empyema fluids (r = 0.80). Chemotactic activity for neutrophils was elevated in empyema fluid and the addition of IL-8 neutralizing serum decreased bioactivity by 32.22%. Malignant pleural effusions had the highest levels of MCP-1 (12.0 +/- 3.7 ng/ml) when compared with others. Cytology-positive pleural fluids (n = 10) had a higher level of MCP-1 than cytology-negative effusions (p = < 0.05). Malignant pleural fluid MCP-1 levels correlated (r = 0.70) with the absolute number of monocytes in the pleural fluid. Neutralization of monocyte chemotactic activity of malignant pleural fluid by specific neutralizing serum caused a 70.3% inhibition of bioactivity. Immunohistochemical staining of malignant pleural fluid localized antigenic MCP-1 to malignant cells. We conclude that both IL-8 and MCP-1 play major but not exclusive roles in the recruitment of neutrophils and monocytes from the vascular compartment to the pleural space.

Topics: Chemokine CCL2; Chemotactic Factors; Cytokines; Empyema; Heart Failure; Humans; Immunohistochemistry; Interleukin-8; Pleural Effusion; Pleural Effusion, Malignant; Pleurisy; Pneumonia; Tuberculosis, Pulmonary

Interleukin-8 (IL-8), a potent neutrophil chemotactic peptide, has been found in association with human disease, but its contribution to chemotactic activity in humans is not yet known. We asked whether IL-8 is present in inflammatory human pleural effusions, and to what extent it contributes to pleural liquid neutrophil chemotactic activity. Because tumor necrosis factor alpha (TNF-alpha) is a strong inducer of IL-8, we also asked whether TNF-alpha was present. For this prospective study, we collected pleural liquid from 51 patients (empyema, 14; parapneumonic, four; tuberculous, eight; malignant, nine; miscellaneous exudative, seven; and transudative, nine), counted pleural neutrophils, and measured IL-8 and TNF-alpha concentrations in the supernatant. To determine the contribution of IL-8 to chemotactic activity in empyema, we measured the neutrophil migration induced by empyemic liquids before and after addition of anti-IL-8 F(ab')2 antibody fragments or control anti-IL-6 F(ab')2. We found that IL-8 concentrations were higher in empyema (61.3 +/- 21.0 ng/ml [SEM]) than in all other effusions (1.1 +/- 0.5 ng/ml) (p = 0.0001). All empyema liquids had IL-8 concentrations above 2.5 ng/ml, which was true for only three of the other 37 effusions (two parapneumonic, one tuberculous). IL-8 levels correlated with the pleural neutrophil count (r = 0.46; p = 0.007) and the neutrophil chemotactic activity of pleural liquid (r = 0.43; p = 0.008). Anti-IL-8 antibodies decreased chemotactic activity in empyema liquids by 65 +/- 5%, whereas the control antibody had no effect (0 +/- 5% decrease) (p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chemotaxis, Leukocyte; Empyema, Pleural; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Pleural Effusion; Prospective Studies; Tumor Necrosis Factor-alpha

Chemotactic activity of protein origin was demonstrated in carrageenan-induced pleural exudates by the chemotactic response of neutrophils in the modified Boyden chamber. The activity was partly neutralized by monospecific antisera to complement component 5 and was destroyed by trypsin and chymotrypsin treatment but it differed from that in rat serum or plasma in that it was stable for 30 min at 56 degrees C. Indomethacin (5 mg/kg i.v.) reduced equally protein content (56%) and total chemotactic activity (58%); i.e., chemotactic activity/mg of exudate protein was unchanged. Intrapleural injection of autologous or homologous serum also induced an infiltration of neutrophils; the protein content of the pleural fluid decreased by 60-70% in 4 h, whereas with carrageenan there was a progressive increase in exudate protein. When serum was injected in two doses to maintain protein levels comparable to those found following carrageenan injection, the number of neutrophils in the exudates was also comparable. In contrast to carrageenan, the response to serum was not inhibited by indomethacin. From these and other data we suggest that the exudate chemotactic activity is generated from plasma protein and that indomethacin acts primarily to reduce extravasation of plasma and consequently generation of chemotactic activity.

Topics: Animals; Blood Proteins; Carrageenan; Chemotactic Factors; Chemotaxis, Leukocyte; Complement C5; Exudates and Transudates; Indomethacin; Interleukin-8; Male; Neutrophils; Pleural Effusion; Rats; Rats, Inbred Strains